DESCRIPTION (Applicant's Description) Colorectal cancer is the second leading cause of cancer death in the United States. There are no curative chemotherapy regimens for metastatic disease. Only two active drugs are available in this disease, illustrating the need for identification and development of new active agents for this malignancy. Perillyl alcohol, an orally administered monoterpene, is presently completing preliminary phase I evaluation at University of Wisconsin. As a class of agents, the monoterpenes are active in several different in vivo and in vitro cancer model systems. They inhibit cellular proliferation, induce differentiation and apoptosis and produce differential gene regulation. Phase I results show that perillyl alcohol can be given at tolerable dose levels on a chronic four times daily schedule. In addition, one patient on the first phase I study has now developed significant regression of metastases from colorectal cancer while receiving perillyl alcohol. Together with preclinical data, this is encouraging for further phase II study of perillyl alcohol in colorectal cancer. The primary goal of this project is to assess the clinical activity of perillyl alcohol in patients with metastatic colorectal cancer. Perillyl alcohol will be administered 4 times daily at an initial dose of 1,200 mg/m2/dose with a possible escalation to 1,600 mg/m2/dose. Measurement of clinical activity will include time to disease progression, disease stabilization and/or response rate and clinical toxicity. Two laboratory correlate Studies will be assessed. Mutations in p53 may confer resistance to perillyl alcohol. Available tumor specimens will be assessed for p53 mutations and correlated, if possible, to drug activity. NQO1 is a gene overexpressed in colorectal cancer that produces an enzyme that metabolizes several drugs, including perillyl alcohol. We will measure serum and tumor NQO1 expression and correlate, if possible, with drug toxicity and efficacy.